Condition category
Cancer
Date applied
27/04/2012
Date assigned
27/04/2012
Last edited
11/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Shama Fernando

ORCID ID

Contact details

Oncology Clinical Trials Office
Department of Oncology
Old Road Campus
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
-
PACMEL@octo-oxford.org.uk

Additional identifiers

EudraCT number

2011-002545-35

ClinicalTrials.gov number

Protocol/serial number

12095

Study information

Scientific title

A randomised phase II study of paclitaxel with or without GSK1120212 in advanced wild type BRAF melanoma

Acronym

PACMEL

Study hypothesis

This is a randomised multi-centre study. 80 patients (forty in each of 2 arms) with melanoma will be randomly assigned to receive treatment with paclitaxel chemotherapy or the same drug along with GSK1120212, a new medicine. To take part the patient's melanoma must have a normal BRAF gene (at V600), which is about 60% of people with melanoma. This can be checked on a sample of the patient's tumour (usually one that has already been taken as part of their treatment). Prior to the randomised part of the study, between 9 and 18 patients will take part in the trial to establish the best dose of GSK1120212 and paclitaxel in combination.

Ethics approval

NRES Committee South Central - Oxford, 23/01/2012, ref: 11/SC/0458

Study design

Randomised interventional phase II trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Melanoma

Intervention

Dose Escalation Phase: Patients with advanced melanoma will be recruited into 3 dose level cohorts. Three dose levels of GSK1120212, starting at 1.0 mg for the first cohort and escalating by 0.5 mg to 1.5 mg and 2.0 mg for the second and third cohorts respectively. At all dose levels, GSK1120212 will be administered once daily orally in combination with an 80 mg/m2 IV infusion of paclitaxel on Days 1, 8 and 15 of each 4 week cycle. This phase will determine the maximum tolerated dose of GSK1120212 in combination with paclitaxel for the randomisation phase. Paclitaxel will be administered for up to 6 cycles, but GSK1120212 may be continued until disease progression or intolerable toxicity.

Randomisation Phase: Two treatment arms:
1. Maximum 6 cycles of single agent Paclitaxel alone as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle
2. Maximum 6 cycles of Paclitaxel as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle in combination with maximum tolerated dose of GSK1120212 once daily orally.
GSK1120212 may be continued until disease progression or intolerable toxicity.

Patients will be followed up every 3 months until disease progression.

Intervention type

Drug

Phase

Phase II

Drug names

GSK1120212, paclitaxel

Primary outcome measures

1. Efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone
2. Progression free survival

Secondary outcome measures

1. Further efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone
2. Overall survival
3. Objectine response rate
4. Progression free survival at 6 months

Overall trial start date

13/04/2012

Overall trial end date

30/04/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged = 18 years
2. Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wild type BRAF status from a sample of melanoma provided for mutational analysis in Oxford (phase 2 part only).
3. Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
4. Measurable disease as defined by RECIST 1.1 (phase 2 part only)
5. ECOG performance score of 0 or 1
6. Life expectancy of at least 12 weeks.
7. Maximum 2 prior lines of treatment for advanced disease.
8. Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram.
9. The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
10. Adequate haematological, hepatic and renal function
11. Target Gender: Male & Female
12. Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 98 - a max of 18 patients will be recruited to the dose escalation phase to determine the max tolerated dose. 80 patients will be recruited into the randomised phase II study

Participant exclusion criteria

1. Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1.
2. Any radiotherapy within 14 days prior to Day 1.
3. Prior taxane or BRAF or MEK inhibitors for metastatic melanoma.
4. Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2.
5. Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy).
6. Grade =2 peripheral neuropathy at study entry.
7. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
8. Known severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL and ethanol
9. Ocular or mucosal malignant melanoma
10. Another active malignancy within the past three years.
11. Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months.
12. Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis.
13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
14. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
15. Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intraocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.

Recruitment start date

20/04/2012

Recruitment end date

30/04/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Oxford
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Headington
Oxford
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

http://www.ox.ac.uk/#http://www.ox.ac.uk/

Funders

Funder type

Industry

Funder name

GlaxoSmithKline (UK)

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/04/2016: No publications found, verifying study status with principal investigator